5CXG

Crystal structure of Mycobacterium tuberculosis KstR in complex with PEG

5CXG の概要

• エントリーDOI: 10.2210/pdb5cxg/pdb
• 関連するPDBエントリー: 3MNL 5CW8
• 分子名称: HTH-type transcriptional repressor KstR, TRIETHYLENE GLYCOL, DI(HYDROXYETHYL)ETHER, ... (4 entities in total)
• 機能のキーワード: transcriptional repressor, tetr family transcriptional repressor, cholesterol catabolism, coa thioester ligand, structural genomics, tb structural genomics consortium, tbsgc, transcription regulator
• 由来する生物種: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 89966.68

構造登録者

Ho, N.A.T.,Dawes, S.,Kendall, S.,Baker, E.N.,Lott, J.S.,TB Structural Genomics Consortium (TBSGC) (登録日: 2015-07-28, 公開日: 2016-02-17, 最終更新日: 2023-09-27)

主引用文献

Ho, N.A.,Dawes, S.S.,Crowe, A.M.,Casabon, I.,Gao, C.,Kendall, S.L.,Baker, E.N.,Eltis, L.D.,Lott, J.S.
The Structure of the Transcriptional Repressor KstR in Complex with CoA Thioester Cholesterol Metabolites Sheds Light on the Regulation of Cholesterol Catabolism in Mycobacterium tuberculosis.
J.Biol.Chem., 291:7256-7266, 2016

PubMed Abstract: Cholesterol can be a major carbon source forMycobacterium tuberculosisduring infection, both at an early stage in the macrophage phagosome and later within the necrotic granuloma. KstR is a highly conserved TetR family transcriptional repressor that regulates a large set of genes responsible for cholesterol catabolism. Many genes in this regulon, includingkstR, are either induced during infection or are essential for survival ofM. tuberculosis in vivo In this study, we identified two ligands for KstR, both of which are CoA thioester cholesterol metabolites with four intact steroid rings. A metabolite in which one of the rings was cleaved was not a ligand. We confirmed the ligand-protein interactions using intrinsic tryptophan fluorescence and showed that ligand binding strongly inhibited KstR-DNA binding using surface plasmon resonance (IC50for ligand = 25 nm). Crystal structures of the ligand-free form of KstR show variability in the position of the DNA-binding domain. In contrast, structures of KstR·ligand complexes are highly similar to each other and demonstrate a position of the DNA-binding domain that is unfavorable for DNA binding. Comparison of ligand-bound and ligand-free structures identifies residues involved in ligand specificity and reveals a distinctive mechanism by which the ligand-induced conformational change mediates DNA release.

PubMed: 26858250
DOI: 10.1074/jbc.M115.707760

実験手法

X-RAY DIFFRACTION (2.1001 Å)